P756: ALLOGENEIC STEM CELL TRANSPLANTATION IN MYELODYSPLASTIC SYNDROME/MYELOPROLIFERATIVE NEOPLASM (MDS/MPN) OVERLAP SYNDROMES. A SINGLE CENTER EXPERIENCE AND DISSECTION OF MUTATIONAL PROFILE
Authors: A. Avendaño Pita, M. Martín Izquierdo, S. Muntión Olave, T. Jímenez Solas, M. García Antúnez, L. Eva, M. Del Rey, S. Toribio Castelló, A. Yeguas Bermejo, T. González, J. M. Hernández-Rivas, A. Á. Martín López, M. Cabrero, E. Pérez López, A. Cabero, M. Baile, L. Vázquez, L. López Corral, F. Sánchez-Guijo, D. Caballero Barrigon, M. Cortés Rodríguez, M. Díez Campelo
Journal: HemaSphere (2022)

Background: MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative in the absence of disease-modifying therapies. Aims: To describe clinical, biological and molecular characteristics at diagnosis and transplant outcomes of our series trying to detect witch parameters may have impact on survival. Methods: We retrospectively reviewed 35 consecutive patients who underwent to allo-HSCT from 1999 to 2021 as MDS/MPNS overlap syndrome. Descriptive statistics and survival analysis were performed trough jamovi (Version 2.2.). Results: Clinical, biological and molecular baseline characteristics are summarized in image. Median age at allo-HSCT were 58 (27-70) with a median time from diagnosis to allo-HSCT of 8 months (1-128). Twenty patients (57%) were referred in complete remission (CR). Preferred graft source were peripheral blood in 34 patients (97.1%). Regarding to conditioning regimen, 26 patients (74.3%) received reduced intensity, 7 patients (20%) received myeloablative and 2 patients (5.7%) sequential conditioning. Eighteen patients (51.4%) had matched sibling donor, 8 patients (22.8%) had matched unrelated donor, 3 patients (8.6%) mismatched unrelated donor and 6 (17.1%) haploidentical donor. All patients reached neutrophil graft and 31 patients (88.6%) reach platelet graft with a median time of 19 (12-29) and 14 (10-36) days respectively. On day +100, 29 patients (82.9%) were in CR, 4 patients (11.4%) did not reach response and 2 (5.7%) were not evaluable. Twenty three patients (65.7%) developed acute graft versus host disease (GVHD), in 19 cases (54.3%) grades II-IV, and 15 patients (42.9%) developed chronic GVHD, in 8 cases (22.9%) moderate-severe grade. Median follow-up were 13 months (2-153) with 17 months (2-153) for chronic myelomonocitic leukemia (CMML) and 11.5 months (2-133) for atypical chronic. myeloid leukemia (aCML). Overall survival (OS) at 1, 3, and 5 years were 69.7%, 54.9% and 42.5% respectively. Sixteen patients (45.7%) relapsed with a median time of 7.5 months (0-85). Among relapsed patients, 5 patients (31.3%) were not treated, 3 patients (19.8%) received donor lymphocyte infusion, in 5 patients (31.3%) we administered hypometilating agents and salvage chemotherapy in 2 (12.5%) remaining patients reaching second allo-HSCT in two cases. Non-relapse mortality were 31.4%, in most cases due to infection. Transplant related mortality (TRM) at day +100 and global TRM were 5.7% and 14.3% respectively. At last follow-up, 13 patients (37.1%) remain alive, 11 (31.4%) in CR and 2 (5.7%) in relapsed situation. On the univariate analysis, harboring signal transduction mutation (p = 0.008), mutational global burden by variant allelic frequency (VAF) at diagnosis greater than 30% (p = 0.045) were asociated with worse outcomes. On the other hand, reaching CR at day +100 (p <0.0001) and developing chronic GVHD (p = 0.0001) seems to improve survival. If we look at the CMML subgroup, we found that new CMML transplant score significantly stratifies outcomes (p = 0.006). Image:Summary/Conclusion: Once again, poor results are confirmed for this MDS/MPN overlap syndromes with only a third of the patients being long term survivors. Molecular data offered by NGS may help to refine prognostic scores and to stablish transplant referral. Mutations in signaling pathways seems to confer poor prognosis as a late event in disease course and provide more aggressive clinical behavior.